title: Artesunate exerts specific cytotoxicity in retinoblastoma cells via CD71.
abstract: Retinoblastoma (RB) is an intraocular cancer that affects young children. There is an ongoing effort to find new agents for RB management that are effective, specific and with few side-effects. In the present study, we tested artesunate (ART), a synthetic derivative from the herbal drug artemisinin, used in the clinic for the treatment of malaria. We analyzed ART cytotoxicity in an RB cell line (RB-Y79) and in a retinal epithelial cell line (hTERT-RPE1) by flow cytometric analysis (FCM). We related the effect of ART to the expression of transferrin receptor 1 (TfR-1, also known as CD71) by knocking down CD71 with RNAi and analyzing cell cycle variables by FCM. We found that the cytotoxic action of ART is specific for RB cells in a dose-dependent manner, with low toxicity in normal retina cells. ART is more effective in RB than carboplatin with a markedly strong cytotoxic effect on carboplatin-resistant RB cells. RB had higher CD71 levels at the membrane compared to normal retinal cells. We showed that ART internalization in RB cells is dependent upon the expression of the CD71. In addition, ART blocked the cell cycle progression at the G1 phase, even at low doses, and decreased the proportion of RB cells in the S phase. In conclusion, we showed that ART is a promising drug exhibiting high selective cytotoxicity even against multidrug-resistant RB cells. Thus, we suggest that ART could be used in the treatment of RB.
authors.affiliation: Graduate Division, Xuzhou Medical College, Xuzhou, Jiangsu 221004, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhao
authors.forename: Han
authors.initials: H
authors.lastname: Wang
authors.forename: Patricilia
authors.initials: P
authors.lastname: Kunda
authors.forename: Xuemei
authors.initials: X
authors.lastname: Chen
authors.forename: Qiu-Ling
authors.initials: QL
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D000962:Antimalarials / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects*; D019306:Artemisia / Q000737:chemistry; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D015153:Blotting, Western; D016190:Carboplatin / Q000494:pharmacology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011990:Receptors, Transferrin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019572:Retinal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D012175:Retinoblastoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; D000962:Antimalarials; D000970:Antineoplastic Agents; D037621:Artemisinins; C068126:CD71 antigen; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011990:Receptors, Transferrin; D016160:Retinoblastoma Protein; D000077332:Artesunate; D016190:Carboplatin